The objectives of this project are twofold - 1) to determine the factors that control the movement of solute and water across the lung epithelium and 2) to elucidate the effects of airborne metals such as mercury and cadmium and of products of ozone oxidation on these control mechanisms. Two biological preparations, the amphibian lung and the perfused, microlavaged, mammalian alveolar sac, will be utilized to pursue the objectives. Fluxes of ions, water and heavy metals across the entire lung wall and the luminal membrane of the alveolar epithelial cells will be measured in the excised bullfrog lung mounted as a planar sheet or as a sac. The effect of sulfhydryl compounds, EDTA, imidazoles and antioxidants on metal binding and on metal and ozonide-induced permeability changes will be measured in the intact, excised lung and in epithelial cells separated by enzymatic procedures. Similar measurements will be made by micropuncture techniques on the mammalian alveolar sac. Differences in the patterns of heavy metal protection afforded by luminal and blood-borne complexing agents may make it possible to differentiate between vascular and epithelial sites of metal action. In addition, changes in the pattern of response to heavy metals in lungs from animals with a surfeit or deficit of essential substances such as zinc, selenium and vitamin E may help identify cellular constituents that prctect against lung damage.